At birth, the average human scalp has approximately 100,000-150,000 hair follicles. Initially, hair follicles normally exhibit fine lanugo hair shafts, which are commonly referred to as "baby hair". This lanugo hair "matures" eventually, into terminal hair shafts, which is the hair most often exhibited during adolescence and adulthood. Thereafter, this terminal hair may remain as such, or it may develop into non-terminal vellus hair, which is commonly referred to as a "thinning" of the hair and, in more advanced stages, baldness.
The precise mechanism that triggers the development of non-terminal vellus hair is not precisely understood or agreed upon. However, there have been numerous attempts to provide an effective safe prophylaxis to arrest development of non-terminal vellus hairs and even to stimulate the regeneration of these vellus hairs into terminal hair shafts. Unfortunately, none of these attempts have proven to be fully satisfactory.
Thus, it can be seen that there remains a need for compositions, medicaments, and methods for administering the same, which are effective in stimulating the development of terminal hairs from non-terminal vellus hairs, are safe for use with a human host, and which are easy to administer.
There are many causes of hair loss for which suitable treatments are well known. For example, if the hair loss is due to general poor health of the patient, then a program designed to improve overall health would be instituted. If the patient's dietary habits are the cause of hair loss, then the patient's diet should be changed. If the patient's medications have the side effect of hair loss, then the medications should possible be changed. If a patient's shampoo is the cause of the hair loss, then the shampoo should be changed. If the patient's hair loss can be attributed to certain types of stress, then those types of stress should be eliminated or reduced. A patient's hair loss may be attributable to certain underlying dermatological conditions such as psoriasis, seborrheic dermatitis, perifolliculitis capitis, pseudopelade of Brocq (alopecia cicatricata), lichenplanopilaris, fungal and bacterial infections, connective tissue diseases such as lupus erythematosus, scleroderma, sarcoidosis, genetic abnormalities (including ectodermal dysplasia) among others.
A patient's hair loss may be attributable to certain underlying symptomatic conditions or drug exposure, such as telogen effluvium and anagen effluvium. The compositions and methods of the invention may be employed to supplement or augment known treatments for such conditions.
Telogen effluvium is hair loss that often results in three to six months after a serious illness such as pneumonia, a life-threatening illness, a surgical intervention, or other illness that requires a person to spend an unusually large amount of time in bed rest. Telogen effluvium generally self corrects from three to six months after its onset.
Anagen effluvium is hair loss that results when patients are administered chemotherapeutic agents, or other toxic agents. It is theorized that anagen effluvium is caused by a sudden shock to hair generating tissues (hair bulbs) in the growing state that can result from the administration of chemotherapeutic agents. As a result of the shock, the growing hairs fall out of the hair follicles.
If the patient's hair loss is due to hypothyroidism, then increased thyroid hormones can be administered. If perceived hair loss is due to hyperthyroidism, then the patient's thyroid activity can be reduced by drug therapy. It is noted that hypothyroidism diminishes the amount of hair that will grow because of decreased metabolic rates. Hyperthyroidism causes hairs to become very fine, and the very fine hairs are perceived to be hair loss.
To determine specific known causes of hair loss, a history is taken, and a physical examination is conducted. Once a known cause of hair loss is diagnosed for which a known treatment is accepted, then the known treatment can be instituted.
However, even with types of hair loss whose cause is determined and whose treatment is known, the rate of return of the lost hair may often be undesirably slow. It would be desirable, therefore, to be able to treat the patient being treated for a known cause of hair loss to accelerate the return of hair to such patients.
There are other types of hair loss for which the causes are less well understood, and only a few and limited known effective treatments are accepted in medical practice, i.e., the use of topical minoxidil. For these types of hair loss, the need for alternate effective treatments is very strong. Some examples of hair loss for which satisfactory treatments are not currently available include: male androgenetic alopecia and female androgenetic alopecia (male and female pattern baldness).
Another form of alopecia, known as alopecia areata (including alopecia totalis and alopecia universalis), is a type of hair loss for which no single or multiple treatment modalities (even including minoxidil) are considered to be highly effective.
As further background, it is noted that some vasodilators have been tried topically to treat hair loss, and these vasodilators have not been effective. For example, diazoxide has been tried topically on the scalp to promote hair growth, but this was not deemed to be effective.
It would be desirable to provide effective topical treatments of the hair loss conditions for which satisfactory topical treatments are not currently available.
A number of patents and publications have been uncovered which may be relevant to the scalp treatment methods and compositions of the invention set forth hereinbelow. These patents and publication are as follows, in approximate chronological order:
1. French patent No. 336,814 of Ascoli (1904) PA1 2. New York State Journal of Medicine, Vol. 49, (1949), pages 1317-1318 PA1 3. Aslan A: Med. Klin.: 52, 1758, 1759, 1760 (1957) PA1 4. Scholzel, P.: Med. Klin.: 53, 2239 (1958) PA1 5. French patent No. 1439833 of Serviere (1966) PA1 6. U.S. Pat. No. 3,644,364 of Anthony (1972) PA1 7. Chemical Abstracts No. 79:23508s (1973) PA1 8. French patent No. 72.39675 of Indaly Oy (1973) PA1 9. UK patent No. 1 354 446 of Indal Oy (1974) PA1 10. U.S. Pat. No. 3,896,238 of Smith (1975) PA1 11. U.S. Pat. No. 3,903,256 of MacMillan et al (1975) PA1 12. U.S. Pat. No. 3,952,099 of Smith (1976) PA1 13. Merck Index of Chemicals and Drugs, hereinafter "Merck", 9th Edition, Merck & Co., Rahway, N.J., (1976), entries 6340 and 6343. PA1 14. U.S. Pat. No. 4,139,619 of Chidsey (1979) PA1 15. U.S. Pat. No. 4,150,114 of Smith (1979) PA1 16. UK patent no. 1 603 639 of Haggar (1981) PA1 17. Chemical Abstracts No. 96:74505x (1981) PA1 18. Current Therapy, (1981), page 662 PA1 19. U.S. Pat. No. 4,329,338 of Szego et al (1982) PA1 20. Japanese application no. 58-103310 of Yoshiya (1983) PA1 21. Conn's Current Therapy, 1984, entry on "Alopecia", by Gonzalez et al, pages 599-603. PA1 22. Chemical Abstracts No. 104:24067u (1985) PA1 23. EPO Patent No. 0 158 090 of Roshdy (1985) PA1 24. U.S. Pat. No. 4,596,812 of Chidsey et al (1986) PA1 25. EPO application No. 0 188 793 of Gans et al (1986) PA1 26. UK patent application No. 2 176 104A of Grollier (1986) PA1 27. UK patent application No. 2 177 919A of Salim (1987) PA1 1. French patent No. 336,814 of Ascoli (1904) appears to disclose a composition used to promote hair growth. The composition appears to disclose the active ingredient to be the chlorhydrate of cocaine. The carrier appears to be a grease, such as vaseline, to form a pomade. PA1 2. New York State Journal of Medicine, Vol. 49, (1949), pages 1317-1318, discloses a solution of niacin and procaine hydrochloride that is used for intravenous administration to treat a number of conditions listed in Table 1. The conditions listed include traumatic, degenerative, inflammatory, and miscellaneous conditions, none of which include hair loss. The composition was administered in an isotonic saline solution. There is a disclosure that niacin or nicotinic acid has a vasodilating effect, especially upon the capillary bed. PA1 3. Aslan A, in Med. Klin.: 52, 1758, 1759, 1760 (1957), appears to disclose, as indicated in the translation of the Scholzel article referred to below, that procaine has been used in injection or intravenous therapy of old people resulting in better mental and physical performance abilities, increase in muscle strength, improvement of rigidity, and stimulation of hair growth in many cases of baldness. PA1 4. Scholzel, P., in Med. Klin.: 53, 2239 (1958), in an English translation of the article in German, discloses the general content of the Aslan article mentioned above and goes on to disclose findings relating to a specific patient who, after 40 years of alopecia, showed hair growth after intravenous procaine therapy. There is also a disclosure that a person named Kohler, reported in 1957, the use of a combination of procaine with various vitamins in an apparently injectable composition ("Gerioptil pro injectione"). However, the specific use of effects of the Kohler compositions were not disclosed. PA1 5. French patent No. 1439833 of Serviere (1966) appears to disclose a composition which contains a synergistic combination of the following ingredients: malic acid, procaine, and a soluble derivative of sulfapyridine. The composition is apparently applied topically to improve hair characteristics, but not necessarily hair growth. PA1 6. U.S. Pat. No. 3,644,364 of Anthony (1972) discloses a process for preparing compounds which include minoxidil, an agent that may promote hair growth. PA1 7. Chemical Abstracts No. 79:23508s (1973) discloses an abstract of a German patent (to Indal Oy) that discloses hair growth promoting characteristics. The disclosures in the German patent of Indal Oy appear to be similar to the disclosures in French patent no. 72.39675 of Indal Oy (1973) and UK patent no. 1 354 446 of Indal Oy (1974) mentioned below. PA1 8. French patent No. 72.39675 of Indal Oy (1973) appears to disclose the compositions that are disclosed in UK patent no. 1 354 446 of Indal Oy (1974). PA1 9. UK patent No. 1 354 446 of Indal Oy (1974) discloses a composition for promoting the growth of hair. The composition contains nicotinic acid and salicylic and/or benzoic acid dissolved in a carrier containing ethanol, urea, polyoxyethylene sorbitan-monopalmitate or monostearate, with the remainder being isopropyl myristate. PA1 10. U.S. Pat. No. 3,896,238 of Smith (1975) discloses compositions for enhancing the penetration of pharmacologically active agents through skin comprising a sugar ester in combination with a sulfoxide or phosphine oxide. In Example VI, a topical anesthetic composition is disclosed for use in a spray can. The composition contains 1% benzocaine and 0.15% decyl methyl sulfoxide in a carrier comprised of approximately 50% ethanol and approximately 50% of a spray can propellant. There is a disclosure that the benzocaine can be replaced by an equivalent amount of procaine hydrochloride. PA1 11. U.S. Pat. No. 3,903,256 of MacMillan et al (1975) discloses compositions for topical application to skin comprising a sunscreen in certain aliphatic sulfoxides which enhance the penetration of the sunscreens through the skin. Example IV discloses a topical local anesthetic comprised of procaine hydrochloride, nonyl methyl sulfoxide, and the balance water. PA1 12. U.S. Pat. No. 3,952,099 of Smith (1976) is very similar in its disclosure to the above-mentioned U.S. Pat. No. 3,896,238 of Smith (1975). PA1 13. Merck Index of Chemicals and Drugs, hereinafter "Merck", 9th Edition, Merck & Co., Rahway, N.J., (1976), entries 6340 and 6343. PA1 14. U.S. Pat. No. 4,139,619 of Chidsey (1979) discloses compositions which employ minoxidil in carriers to be applied topically to a scalp to promote hair growth. PA1 15. U.S. Pat. No. 4,150,114 of Smith (1979) is very similar in its disclosure to the above-mentioned U.S. Pat. No. 3,896,238 of Smith (1975). PA1 16. UK patent No. 1 603 639 of Haggar (1981) discloses a composition for application to the hair and scalp for use in stimulating hair growth in treating alopecia and excessive hair loss. The composition includes a hair conditioner (lotion or cream) and a vitamin solution which contains vitamins B1, B2, B6, A, D, nicotinamide, and ascorbic acid. It has been found particularly advantageous to use Oil of Rosemary in the vitamin solution. More specifically, in one preferred embodiment, Oil of Rosemary is included. In another preferred embodiment, Oil of Balsam is included. In addition, the carrier can be the conditioner LIFE-TEX (T.M.) produced by Wella, which has been found satisfactory. The carrier desirably promotes absorption into the scalp and is preferably an antiseptic type spirit which may be alcohol, isophane insulin, or other biologically acceptable volatile liquid. However, white iodine is the preferred carrier. Petroleum jelly or liquid paraffin may also be included. There is a statement that the composition for application to the hair and scalp includes a commercial hair conditioner and a vitamin solution which contains one or more of the disclosed vitamins. PA1 17. Chemical Abstracts No. 96:74505x (1981) discloses an abstract of the UK Haggar patent discussed above. PA1 18. Current Therapy, (1981), page 662, discloses, that in the case of alopecia areata, single patches frequently regrow spontaneously within a few months although the course is unpredictable (including the rare extension to alopecia totalis or alopecia universalis), and recurrences are common. PA1 19. U.S. Pat. No. 4,329,338 of Szego et al (1982) discloses compositions for use as cosmetics. The compositions include a reaction product of nicotinic acid, a nicotinic acid salt, or a nicotinic acid halide and a polyhydroxy compound whose general formula is given in the Abstract. The active agents are disclosed as exerting beneficial effects for stimulating scalp or hair bulbs. PA1 20. Japanese application No. 58-103310 of Yoshiya (1983), in an English language Abstract, discloses a composition for accelerating hair growth that includes ginger in an alcoholic carrier which includes methyl alcohol, ethyl alcohol, and other lower alcohols. PA1 21. Conn's Current Therapy, 1984, entry on "Alopecia", by Gonzalez et al, pages 599-603, discloses a classification of causes of alopecia. Two main categories are nonscarring alopecia and scarring alopecia. Both the nonscarring alopecia and the scarring alopecia are subdivided into more specific conditions. See Table 1 on page 599. PA1 22. Chemical Abstracts No. 104:24067u (1985) discloses hair preparations for the promotion of hair growth which include extracts of the Acanthopanax root bark, with or without peripheral circulation promoting substances which include nicotinic acid. PA1 23. EPO Patent No. 0 158 090 of Roshdy (1985), written in the German language, appears to disclose compositions which contain vitamin C, vitamin A, vitamins of the B series, phospholipids, and unsaturated fatty acids. The compositions can be used in carriers that include alcohol or isopropyl alcohol. Other components of the compositions may include lecithin, amino acids, UV stabilizers, or antihistamines. PA1 24. U.S. Pat. No. 4,596,812 of Chidsey et al (1986) discloses methods and compositions for treating male pattern alopecia. The compositions include the substance known as minoxidil. Minoxidil is disclosed as a vasodilator that functions to dilate the peripheral vascular system. Minoxidil compositions are applied topically to the scalp and are used in a carrier system which can include equal parts of ethyl alcohol and propylene glycol. PA1 25. EPO application No. 0 188 793 of Gans et al (1986) discloses compositions containing minoxidil that include a carrier containing 70% alcohol, 20% water, and 10% propylene glycol. In this patent, an improvement comprises the inclusion of a hydroxy (lower alkyl) acrylate polymer to retard seepage of the minoxidil beyond the application site. PA1 26. UK patent application No. 2 176 104A of Grollier (1986) discloses compositions for the treatment of hair and of the scalp to promote fresh hair growth. It is disclosed that compositions containing nicotinic acid or its esters, when applied to the scalp, have rubefacient and vasodilant activity. The specific compositions disclosed in this patent include the combination of certain water-soluble polyamides of the poly-beta-alanine type with nicotinic acid or its esters. As shown in Examples 1 and 4, for a hair-care lotion, the carrier includes ethyl alcohol and water. PA1 27. UK patent application No. 2 177 919A of Salim (1987) discloses, in Example 9, a topical preparation to restore hair growth to areas of the human scalp suffering from hair loss. The preparation includes procaine, a physiologically acceptable, organic, in vivo sulphydryl group releasing agent, and castor oil.
More specifically, with respect to the references listed above, the following summaries of their disclosures are provided.
Entry 6340 is for nicotinamide. PA2 Entry 6343 is for nicotinic acid also known as niacin. Nicotinic acid is soluble in propylene glycol.
The following conclusions can be made from a consideration of the prior art discussed above. Procaine has been used topically, in the presence of other active ingredients and in the presence of complex carrier ingredients, often including sulfur-containing carriers, to treat the scalp for hair growth. It is also clear from the prior art that neither procaine nor niacin, either alone or in combination with one another, has been used topically without other active ingredients and without a complex carrier system which often includes sulfur-containing carriers and non-hydrophilic ingredients.
Carriers containing sulfur-containing ingredients have their problems. For example, the safety and efficacy of dimethylsulfoxide (DMSO) has not been sufficiently established to for the U.S. Food and Drug Administration to permit its use in the United States.
Carriers containing non-hydrophilic ingredients may have the undesirable property of impeding or preventing penetration of the active, hair-bulb treating agents into the hair bulb from the surface of the skin when the active ingredient is applied topically.